Separate promoters from proximal and medial control regions contribute to the natural killer cell-specific transcription of the human Fc gamma RIII-A (CD16-A) receptor gene

The molecular events governing the differentiation pathway of natural killer (Mt) cells are not well understood. The phenotype of mature NK cells is specified by the expression of the low affinity Fc receptor for IgG (human Fc gamma RIII, CD16) encoded by the Fc gamma RIII-A gene. Here we report that the Pprox promoter (-198/-10) of Fc gamma RIII-A stimulated by its own intron enhancer (+10/+712) was only one of the cis-elements that target the expression of a reporter gene in the immature NK cell line, YT. The transcription start sites of the Fc gamma RIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial -1817/-850 Fc gamma RIII-A control region. Two promoters, Pmedl (-942/-850) and Pmed2 (-1376/-1123) resided in this region and controlled for the initiation of these transcript classes encoding the known Fc gamma RIII-A receptor protein. Deletion mapping studies demonstrated that the 93 base pairs -942/-850 Pmedl sequence was sufficient to confer cell type specific expression in YT cells. The 5' end of Pmedl (-942 to -921) was required for full promoter function indicating the presence of an important sequence motif recognized by a YT-specific factor. Our data suggest that this motif might be a useful tool for subsequent identification of putative transcription factors uniquely active in YT and Nh cells.